User:Cwebb2023/Prenatal testing

Edits

Synonyms: Genetic Testing

Purpose: To monitor maternal and fetal health and progression, as well as, detect fetal abnormalities during pregnancy.

Additions to Intro Section (I may remove some of previous persons stuff if it is repetitive or has changed since then)

Nearly every pregnant individual undergoes some type of prenatal testing. There are varying levels of simplicity, invasiveness, risk, and information that correlate to each test. These tests can be as basic as taking the mothers weight (routine) to as complex and invasive as taking internal fetal blood samples for chromosomal analysis (genetic). Routine tests are conducted repeatedly throughout an individual’s pregnancy at prenatal checkups to monitor health and progression of the mother and the baby. Genetic testing is now a common practice offered to pregnant women by their healthcare professional at specific stages of their pregnancy to test for birth defects and chromosomal abnormalities, or the possibility of carrying these genetic traits. Testing capabilities and practices are becoming safer and less invasive as this area of research continues to evolve.

Prenatal genetic testing is optional for every individual with various advantages and disadvantages, depending on the patient. As women age, the potential of conceiving a child with birth defects increases, therefore prenatal genetic testing is more encouraged to mothers over the age of 35. They are also recommended for individuals that have a family history of medical conditions. The results of these tests provide awareness and enable advance planning and preparation, particularly if the potential diagnosis would require special care or could cause complications during delivery. This is a key reason that some individuals choose to undergo testing. Varying levels of procedural risk, as well as different religious, moral, and/or conscious beliefs may deter a parent from prenatal testing. An individual can conduct online research and/or discuss their options with a healthcare professional to make a personally informed decision about prenatal genetic testing when it is offered.

Additions to Purpose Section (I may delete some of the invasiveness information since all of the tests aren’t solely based on invasiveness. I feel as though it should be more focused on the testing, however I did redo the table in this section – see attached Excel spreadsheet – to still include whether the test is invasive or not)

Prenatal genetic testing can identify various chromosomal abnormalities, autosomal conditions, various birth defects, and some fetal blood disorders.

Chromosomal abnormalities result from an abnormal number or structuring of chromosomes. This includes chromosomal deletions, duplications, inversions, and translocations. Some examples of chromosomal abnormalities include:

-       Down syndrome (trisomy 21)

-       Edwards syndrome (trisomy 18)

-       Patau syndrome (trisomy 13)

-       Turner syndrome (monosomy X)

-       Klinefelter (XXY) syndrome

-       Trisomy X (XXX) syndrome

-       XYY syndrome

-       Pallister Killian syndrome

-       Wolf-Hirschhorn syndrome

-       Cri-du-chat syndrome

-       WAGR syndrome

-       DiGeorge syndrome

-       Fragile X syndrome

-      Prader-Willi/Angelman Syndrome

Autosomal recessive conditions occur when both parents pass on a mutation within an autosomal (non-sex) chromosome. Some examples of autosomal recessive conditions are:

-       Cystic fibrosis

-       Sickle cell anemia

-       Tay Sachs disease

-       Spinal muscular atrophy

-       Autosomal recessive polycystic kidney disease

-       Phenylketonuria

Neural tube defects are a type of birth defect that occurs when the neural tube of a fetus does not form/close properly, potentially effecting other systems throughout the body. Some examples of neural tube defects are:

-       Spina bifida

-       Anencephaly

-       Encephalocele

-       Tethered spinal cord syndrome

Abdominal wall defects are a type of birth defect that occur when the abdominal wall of a fetus does not form properly, potentially effecting other organs throughout the body. Some examples of abdominal wall defects are:

-       Gastroschisis

-       Omphalocele

-       Bladder exstrophy

-       Cloacal exstrophy

-       Ectopia cordis

-       Pentalogy of Cantrell

-       Body-stalk anomaly

Blood disorders can occur from a negative interaction between the maternal blood and the fetal blood. An example of a fetal blood disorder is Hemolytic disease of the fetus.

Edit in section title

Prenatal Genetic Testing and Screening: Detecting Chromosomal Abnormalities
Additions to Screening for Chromosomal Abnormalities Section

Prenatal genetic testing is done by means of different screens and diagnostic tests. A screen informs an individual of the potential for certain abnormalities occurring, whereas, the diagnostic testing is used to confirm/diagnose specific abnormalities exist within the fetus. Prenatal screens are typically less invasive than prenatal diagnostic tests. They come with much lower risk, however, the results are not as definitive as diagnostic tests. Providers often recommend following up with a diagnostic test upon receipt of a positive result from a specific screen.

Medically invasive techniques are those in which a tool is used to access something inside the body. There are varying degrees of invasiveness, depending on what specimen is required to complete the test. The typical blood draw administered by a healthcare professional is one of the most common invasive medical practices. Since it causes minimal discomfort and there is very low risk associated with the sample collection, a blood draw is considered less invasive. Chorionic villus sampling (CVS) and Amniocentesis are the most invasive prenatal tests because there is greater associated risk and the sample is more difficult to access. These procedures are done via needle insertion into the abdomen in order to collect a sample within the uterus, meaning exceptional care/precision is required.

Previous Information – no major edits here

Ultrasound imaging and serum markers as indications for genetic testing[edit]
Ultrasound imaging provides the opportunity to conduct a nuchal translucency (NT) scan screening for chromosomal abnormalities such as Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and Patau syndrome (trisomy 13). Using the information from the NT scan the mother can be offered an invasive diagnostic test for fetal chromosomal abnormalities. Serum markers are utilized in a similar fashion to identify gestations that should be recommended for further testing. When the NT scan or serum markers arouse suspicion for chromosomal abnormalities the following genetic tests may be conducted on fetal or placental tissue samples: Interphase-fluorescence in situ hybridization (FISH), quantitative PCR and direct preparation of chromosomes from chorionic villi.

''Addition of Screens and Diagnostic Tests Subsections that fall under Prenatal Genetic Testing/Screening. I added everything in red, moved the previous Technique section down, and added to that, as well.''

Carrier Screening
Carrier Screening is a general DNA test that uses a blood or cheek swab sample to determine if the parents carry certain genetic conditions. This test can be done anytime, whether the individual(s) are considering starting a family or have already become pregnant. Various types of carrier screens are available that test for progressively more genetic abnormalities. The single gene/condition screen will test for a specific condition, whereas, the expanded carrier screen will test for hundreds of different abnormalities that can be inherited by a fetus. There are also three gene/condition and ethnic specific carrier tests. In the case of a positive test result, further testing is often recommended, as the carrier test only determines if the parent(s) is a carrier, not if the gene has definitively been passed to the fetus.

Fetal Cell-Free DNA (cfDNA)/Non-Invasive Prenatal Test (NIPT)
Fetal cell-free DNA testing allows for the detection of apoptotic fetal cells and fetal DNA circulating in maternal blood for the noninvasive diagnosis of fetal aneuploidy. A meta-analysis that investigated the success rate of using fetal cell-free DNA from maternal blood to screen for aneuploidies found that this technique detected trisomy 13 in 99% of the cases, trisomy 18 in 98% of the cases and trisomy 21 in 99% of the cases. Failed tests using fetal cell-free DNA are more likely to occur in fetuses with trisomy 13 and trisomy 18 but not with trisomy 21. Previous studies found elevated levels of cell-free fetal DNA for trisomy 13 and 21 from maternal serum when compared to women with euploid pregnancies. However, an elevation of cell-free DNA for trisomy 18 was not observed. Circulating fetal nucleated cells comprise only three to six percent of maternal blood plasma DNA, reducing the detection rate of fetal developmental abnormalities. Two alternative approaches have been developed for the detection of fetal aneuploidy. The first involves the measuring of the allelic ratio of single nucleotide polymorphisms (SNPs) in the mRNA coding region in the placenta. The next approach is analyzing both maternal and fetal DNA and looking for differences in the DNA methylation patterns.

First/Second/Third Trimester Screen
The first, second, combined, and third trimester screens typically consist of an ultrasound (abdominal and/or transvaginal) and maternal blood/serum testing. The ultrasound is used to visually assess the growth, development, and activity of the fetus through imaging observations and measurements. The ultrasound portion of the first trimester screen can include a nuchal translucency screen and a fetal nasal bone determination screen. The available blood tests from the first trimester screen can test for plasma protein A and human chorionic gonadotropin. The second trimester screen looks at specific blood markers, to include the estriol, inhibin and human chorionic gonadotropin hormones and often consists of Alpha-fetoprotein (AFP) screening. Any abnormal results from these screening tests can indicate the possibility of abnormal conditions such as Trisomy 18, Trisomy 21 (Down syndrome), and spina bifida.

Alpha-fetoprotein (AFP)/Multiple Marker Test
The AFP test is often done in the second trimester using the serum from the maternal blood draw. This test looks at a specific protein that is formed in the liver of the fetus and released into the fluid contents of the womb, which is then absorbed into the mother’s blood stream. Multiple determinations stem from the results of AFP testing. Genetically, it can expose chromosomal and neural defects.

Chorionic Villus Sampling (CVS)
CVS is an invasive diagnostic test that can be done during the first trimester of pregnancy for individuals that are looking to identify or are at higher risk of passing chromosomal abnormalities. A tissue cell sample of the placenta is obtained abdominally via needle or via vaginal insertion of a catheter/syringe into the cervix in combination with ultrasound to guide the procedure. Positive results from CVS require blood testing for confirmation.

Amniocentesis
Amniocentesis is an invasive diagnostic test that can be done during the second trimester of pregnancy for individuals that are looking to identify or are at higher risk of passing chromosomal and/or neural tube abnormalities. The procedure is typically done via needle, in combination with ultrasound for guidance, to obtain a sample of the amniotic fluid surrounding the fetus.

Cordocentesis/Percutaneous Umbilical Blood Sampling (PUBS)
PUBS is an invasive diagnostic test that can be done during the second trimester of pregnancy for individuals that are looking to identify or are at higher risk of passing chromosomal and/or blood abnormalities. The demand for cordocentesis tests is diminishing because it has been replaced with CVS and Amniocentesis, which carry less risk. The procedure is typically done via needle into the mother’s abdomen, in combination with ultrasound for guidance, to obtain a blood sample from the umbilical cord of the fetus.

Digital PCR
Recently, it has been proposed that digital PCR analysis can be conducted on fetal cell-free DNA for detection of fetal aneuploidy. Research has shown that digital PCR can be used to differentiate between normal and aneuploid DNA.

A variation of the PCR technique called multiplex ligation-dependent probe amplification (MLPA), targeting DNA, has been successively applied for diagnosing fetal aneuploidy as a chromosome- or gene-specific assay.

Shotgun Sequencing[edit]
Fetal cell-free DNA has been directly sequenced using shotgun sequencing technology. In one study, DNA was obtained from the blood plasma of eighteen pregnant women. This was followed by mapping the chromosome using the quantification of fragments. This was done using advanced methods in DNA sequencing resulting in the parallel sequencing of the fetal DNA. The amount of sequence tags mapped to each chromosome was counted. If there was a surplus or deficiency in any of the chromosomes, this meant that there was a fetal aneuploid. Using this method of shotgun sequencing, the successful identification of trisomy 21 (Down syndrome), trisomy 18 (Edward syndrome), and trisomy 13 (Patau syndrome) was possible. This method of noninvasive diagnosis is now starting to be heavily used and researched further.

Other Techniques[edit]
Microarray analysis, karyotyping, and different genome sequencing techniques are also used to detect abnormalities. Fetal components in samples from maternal blood plasma can be analyzed by genome-wide techniques not only by total DNA, but also by methylated DNA immunoprecipitation (with tiling array), microRNA (such as with Megaplex) and total RNA (RNA-sequencing).

Patient Acceptance[edit]
Research was conducted to determine how women felt about noninvasive diagnosis of fetal aneuploid using maternal blood. This study was conducted using surveys. It was reported that eighty-two percent of pregnant women and seventy-nine percent of female medical students view this type of diagnosis in a positive light, agreeing that it is important for prenatal care. Overall, women responded optimistically that this form of diagnosis will be available in the future.